(2R,8R)-2-(2H-1,3-benzodioxol-5-yl)-6-methyl-3,6,17-triazatetracyclo[8.7.0.0^{3,8}.0^{11,16}]heptadeca-1(10),11,13,15-tetraene-4,7-dione

• ChemBase ID: 699
• Molecular Formular: C22H19N3O4
• Molecular Mass: 389.40396
• Monoisotopic Mass: 389.1375561
• SMILES: O=C1N(CC(=O)N2[C@@H]1Cc1c([nH]c3c1cccc3)[C@H]2c1cc2OCOc2cc1)C
• Canonical SMILES: O=C1N(C)CC(=O)N2[C@@H]1Cc1c([C@H]2c2ccc3c(c2)OCO3)[nH]c2c1cccc2
• InChI: InChI=1S/C22H19N3O4/c1-24-10-19(26)25-16(22(24)27)9-14-13-4-2-3-5-15(13)23-20(14)21(25)12-6-7-17-18(8-12)29-11-28-17/h2-8,16,21,23H,9-11H2,1H3/t16-,21-/m1/s1
• InChIKey: WOXKDUGGOYFFRN-IIBYNOLFSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2R,8R)-2-(2H-1,3-benzodioxol-5-yl)-6-methyl-3,6,17-triazatetracyclo[8.7.0.0^{3,8}.0^{11,16}]heptadeca-1(10),11,13,15-tetraene-4,7-dione; (2R,8R)-2-(2H-1,3-benzodioxol-5-yl)-6-methyl-3,6,17-triazatetracyclo[8.7.0.0^3,^8.0^1^1,^1^6]heptadeca-1(10),11,13,15-tetraene-4,7-dione
• IUPAC Traditional name: tadalafil
• Brand Name: Cialis
• Synonyms: CIA; ICOS 351; Tadanafil; tadalafil; Tadalafil; Cialis; GF 196960; IC 351; Tadalafil(Cialis); (6R,12aR)-6-(1,3-Benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methylpyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione; Tildenafil; UK 336017; Cialis

Database IDs

• CAS Number: 171596-29-5
• MDL Number: MFCD07771966
• PubChem SID: 160964162; 46507646
• PubChem CID: 110635

CALCULATED PROPERTIES

JChem

• Acid pKa: 15.16992
• H Acceptors: 4
• H Donor: 1
• LogD (pH = 5.5): 1.6393403
• LogD (pH = 7.4): 1.6393403
• Log P: 1.6393403
• Molar Refractivity: 104.0816 cm^3
• Polarizability: 41.42806 Å^3
• Polar Surface Area: 74.87 Å^2
• Rotatable Bonds: 1
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.36
• LOG S: -3.19
• Solubility (Water): 2.50e-01 g/l

PROPERTIES

Physical Property

• Solubility: DMSO; Methanol; Practically insoluble in water
• Apperance: White to Off-White Solid
• Melting Point: 276-279°C
• Hydrophobicity(logP): 1.7

Safety Information

• Storage Condition: -20°C; Hygroscopic, -20°C Freezer, Under Inert Atmosphere

Pharmacology Properties

• Target: PDE

Product Information

• Purity: 95+%; 97%; 98%
• Salt Data: Free Base

DETAILS

DrugBank - DB00820

• Drug Groups: approved; investigational
• Description: Tadalafil is an orally adminstered drug used to treat male erectile dysfunction (impotence). It is marketed worldwide under the brand name Cialis. It is a phosphodiesterase 5 (PDE5) inhibitor. Tadalafil's distinguishing pharmacologic feature is its longer half-life (17.5 hours) compared with Viagra and Levitra (4-5 hours). This longer half-life results in a longer duration of action and is, in part, responsible for the Cialis nickname of the "weekend pill." This longer half-life also is the basis of current investigation for tadalafil's use in pulmonary arterial hypertension as a once-daily therapy. [Wikipedia]
• Indication: Used for the treatment of erectile dysfunction.
• Pharmacology: Tadalafil is used to treat male erectile dysfunction (impotence) and pulmonary arterial hypertension (PAH). Part of the physiological process of erection involves the release of nitric oxide (NO) in the corpus cavernosum. This then activates the enzyme guanylate cyclase which results in increased levels of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation in the corpus cavernosum, resulting in increased inflow of blood and an erection. Tadalafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum. This means that, with tadalafil on board, normal sexual stimulation leads to increased levels of cGMP in the corpus cavernosum which leads to better erections. Without sexual stimulation and no activation of the NO/cGMP system, tadalafil should not cause an erection.
• Toxicity: Oral, Rat LD₅₀ = 2000 mg/kg, no deaths or toxicity.
• Affected Organisms: Humans and other mammals
• Biotransformation: Tadalafil is predominantly metabolized by CYP3A4 to a catechol metabolite. The catechol metabolite undergoes extensive methylation and glucuronidation to form the methylcatechol and methylcatechol glucuronide conjugate, respectively. In vitro data suggests the metabolites are not expected to be pharmacologically active at observed metabolite concentrations.
• Absorption: After single oral-dose administration, the maximum observed plasma concentration (Cmax) of tadalafil is achieved between 30 minutes and 6 hours (median time of 2 hours). Absolute bioavailability of tadalafil following oral dosing has not been determined.
• Half Life: 17.5 hours
• Protein Binding: 94%
• Elimination: Tadalafil is excreted predominantly as metabolites, mainly in the feces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).
• Distribution: * 63 L
• Clearance: * oral cl=2.5 L/hr
• References: Naeije R, Huez S: Expert opinion on available options treating pulmonary arterial hypertension. Expert Opin Pharmacother. 2007 Oct;8(14):2247-65. [Pubmed] ; Burnett AL: Molecular Pharmacotherapeutic Targeting of PDE5 for Preservation of Penile Health. J Androl. 2007 Oct 17;. [Pubmed] ; Guazzi M, Samaja M: The role of PDE5-inhibitors in cardiopulmonary disorders: from basic evidence to clinical development. Curr Med Chem. 2007;14(20):2181-91. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S1512

Research Area: Metabolic Disease
Biological Activity:
Tadalafil (Cialis) is a PDE inhibitor. Tadalafil(Cialis), which has demonstrated a high level of selectivity for PDE5 over the other phosphodiesterases, has shown efficacy in improving erectile function and sexual satisfaction in phase III trials. [1]PDE11A3, PDE11A2, and PDE11A1, which contain progressively shorter N-termini, were more sensitive than PDE11A4 to inhibition by Tadalafil(Cialis). [2]

Toronto Research Chemicals - T004500

Used for the treatment of erectile dysfunction. A phosphodiesterase 5 inhibitor.

REFERENCES

• Naeije R, Huez S: Expert opinion on available options treating pulmonary arterial hypertension. Expert Opin Pharmacother. 2007 Oct;8(14):2247-65. Pubmed
• Burnett AL: Molecular Pharmacotherapeutic Targeting of PDE5 for Preservation of Penile Health. J Androl. 2007 Oct 17;. Pubmed
• Guazzi M, Samaja M: The role of PDE5-inhibitors in cardiopulmonary disorders: from basic evidence to clinical development. Curr Med Chem. 2007;14(20):2181-91. Pubmed
• Pomerol et al. Drugs Today. 2003; 39(2): 103
• Carrier, S., et al.: Can. J. Urol., 10(1)
• 12 (1)
• Doggrell, S.A., et al.: Expert Opin. Pharmacother., 6, 75 (1)
• Forgue, S.T., et al.: Br. J. Clin. Pharmacol., 61, 280 (1)